Phenotypic Plasticity – Alternate Transcriptional Programs Driving Treatment Resistant Prostate Cancer

Jagpreet Singh Nanda, Praveen Koganti, Graziela Perri, Leigh Ellis

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Androgen deprivation therapy (ADT) that antagonizes androgen receptor (AR) signaling has made significant increases to overall survival of prostate cancer patients. However, ADT is not curative, and patients eventually progress to castration resistant disease (CRPC). It has become evident that a subset of prostate cancers acquire ADT resistance through mechanisms independent of AR alteration or reprogramming of AR signaling. This approximately involves a quarter of prostate cancers progressing on ADT. Collectively, these tumors evolve via phenotypic plasticity and display the activation of developmental and stemness gene signatures as well as transitional programs including an epithelial-mesenchymal phenotype. Currently, no successful treatments exist for prostate cancer patients to inhibit or reverse prostate tumor progression that utilizes mechanisms of epi-plasticity. This overview will discuss epigenetic mechanisms that mediate phenotypic plasticity and the potential for targeting the epigenome to create a novel direction for combination strategies involving epigenetic therapy to provide durable response.

Original languageEnglish
Pages (from-to)45-60
Number of pages16
JournalCritical Reviews in Oncogenesis
Volume27
Issue number1
DOIs
StatePublished - 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, Begell House Inc.. All rights reserved.

Funding

Cedars-Sinai Faculty Start-Up Funds, National Institute of Health Funds, and Department of Defense Prostate Cancer Program Funds (awarded to LE). An Indian American Urological Association Anupam Ted Kedia Research Scholar Award (awarded to JSN). LE reports grants from the National Institute of Health (R01CA207757, R01CA252468, R21CA257484) and the Department of Defense Prostate Cancer Program (W81XWH-20-1-0056). LE reports grants from the National Institute of Health (R01CA207757, R01CA252468,

FundersFunder number
Department of Defense Prostate Cancer ProgramW81XWH-20-1-0056
Department of Defense Prostate Cancer Program Funds
National Institute of Health Funds
National Institutes of HealthR01CA252468, R01CA207757
National Cancer InstituteR21CA257484

    Keywords

    • EZH2
    • Epigenetic Therapy
    • Epigenetics
    • Lineage Plasticity
    • NEPC
    • Prostate Cancer

    Fingerprint

    Dive into the research topics of 'Phenotypic Plasticity – Alternate Transcriptional Programs Driving Treatment Resistant Prostate Cancer'. Together they form a unique fingerprint.

    Cite this